Publication:
Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts

2

Issued Date

2021-12-01

Resource Type

Article

ISSN

22132619
22132600

DOI

10.1016/S2213-2600(21)00365-9

Other identifier(s)

2-s2.0-85120071049

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet Respiratory Medicine. Vol.9, No.12 (2021), 1377-1386

Suggested Citation

Lieuwe D.J. Bos, Michael Sjoding, Pratik Sinha, Sivasubramanium V. Bhavani, Patrick G. Lyons, Alice F. Bewley, Michela Botta, Anissa M. Tsonas, Ary Serpa Neto, Marcus J. Schultz, Robert P. Dickson, Frederique Paulus, J. P. van Akkeren, A. G. Algera, C. K. Algoe, R. B. van Amstel, A. Artigas, O. L. Baur, P. van de Berg, A. E. van den Berg, D. C.J.J. Bergmans, D. I. van den Bersselaar, F. A. Bertens, A. J.G.H. Bindels, M. M. de Boer, S. den Boer, L. S. Boers, M. Bogerd, L. D.J. Bos, J. S. Breel, H. de Bruin, S. de Bruin, C. L. Bruna, L. A. Buiteman-Kruizinga, O. Cremer, R. M. Determann, W. Dieperink, D. A. Dongelmans, H. S. Franke, M. S. Galek-Aldridge, M. J. de Graaff, L. A. Hagens, J. J. Haringman, S. T. van der Heide, P. L.J. van der Heiden, N. F.L. Heijnen, S. J.P. Hiel, L. L. Hoeijmakers, L. Hol, M. W. Hollmann, M. E. Hoogendoorn, J. Horn, R. van der Horst, E. L.K. Ie, D. Ivanov, N. P. Juffermans, E. Kho, E. S. de Klerk, A. W.M.M. Koopman-van Gemert, M. Koopmans, S. Kucukcelebi, M. A. Kuiper, D. W. de Lange, I. Martin-Loeches, G. Mazzinari, D. M.P. van Meenen, L. Morales-Quinteros, N. van Mourik, S. G. Nijbroek, M. Onrust, E. A.N. Oostdijk, F. Paulus, C. J. Pennartz, J. Pillay, L. Pisani, I. M. Purmer, T. C.D. Rettig, J. P. Roozeman, M. T.U. Schuijt, M. J. Schultz, A. Serpa Neto, M. E. Sleeswijk, M. R. Smit, P. E. Spronk, W. Stilma, A. C. Strang, P. R. Tuinman, C. M.A. Valk, F. L. Veen-Schra, L. I. Veldhuis, P. van Velzen, W. H. van der Ven, A. P.J. Vlaar, P. van Vliet, P. H.J. van der Voort, L. van Welie, H. J.F.T. Wesselink, H. H. van der Wier-Lubbers Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts. The Lancet Respiratory Medicine. Vol.9, No.12 (2021), 1377-1386. doi:10.1016/S2213-2600(21)00365-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/77472

Research Projects

Organizational Units

Authors

Journal Issue

Thesis

Title

Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts

Author(s)

Lieuwe D.J. Bos
 Michael Sjoding
 Pratik Sinha
 Sivasubramanium V. Bhavani
 Patrick G. Lyons
 Alice F. Bewley
 Michela Botta
 Anissa M. Tsonas
 Ary Serpa Neto
 Marcus J. Schultz
 Robert P. Dickson
 Frederique Paulus
 J. P. van Akkeren
 A. G. Algera
 C. K. Algoe
 R. B. van Amstel
 A. Artigas
 O. L. Baur
 P. van de Berg
 A. E. van den Berg
 D. C.J.J. Bergmans
 D. I. van den Bersselaar
 F. A. Bertens
 A. J.G.H. Bindels
 M. M. de Boer
 S. den Boer
 L. S. Boers
 M. Bogerd
 L. D.J. Bos
 J. S. Breel
 H. de Bruin
 S. de Bruin
 C. L. Bruna
 L. A. Buiteman-Kruizinga
 O. Cremer
 R. M. Determann
 W. Dieperink
 D. A. Dongelmans
 H. S. Franke
 M. S. Galek-Aldridge
 M. J. de Graaff
 L. A. Hagens
 J. J. Haringman
 S. T. van der Heide
 P. L.J. van der Heiden
 N. F.L. Heijnen
 S. J.P. Hiel
 L. L. Hoeijmakers
 L. Hol
 M. W. Hollmann
 M. E. Hoogendoorn
 J. Horn
 R. van der Horst
 E. L.K. Ie
 D. Ivanov
 N. P. Juffermans
 E. Kho
 E. S. de Klerk
 A. W.M.M. Koopman-van Gemert
 M. Koopmans
 S. Kucukcelebi
 M. A. Kuiper
 D. W. de Lange
 I. Martin-Loeches
 G. Mazzinari
 D. M.P. van Meenen
 L. Morales-Quinteros
 N. van Mourik
 S. G. Nijbroek
 M. Onrust
 E. A.N. Oostdijk
 F. Paulus
 C. J. Pennartz
 J. Pillay
 L. Pisani
 I. M. Purmer
 T. C.D. Rettig
 J. P. Roozeman
 M. T.U. Schuijt
 M. J. Schultz
 A. Serpa Neto
 M. E. Sleeswijk
 M. R. Smit
 P. E. Spronk
 W. Stilma
 A. C. Strang
 P. R. Tuinman
 C. M.A. Valk
 F. L. Veen-Schra
 L. I. Veldhuis
 P. van Velzen
 W. H. van der Ven
 A. P.J. Vlaar
 P. van Vliet
 P. H.J. van der Voort
 L. van Welie
 H. J.F.T. Wesselink
 H. H. van der Wier-Lubbers

Other Contributor(s)

Department of Medicine, The University of Chicago
 University of Melbourne
 University of Michigan, Ann Arbor
 Washington University School of Medicine in St. Louis
 Monash University
 Hospital Israelita Albert Einstein
 Mahidol University
 Nuffield Department of Medicine
 Emory University
 Amsterdam UMC

Abstract

Background: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches. Methods: PRoVENT–COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342. Findings: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0–15 vs 5, 0–17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17–2·29 for ventilatory ratio; 1·82, 1·24–2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87–11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05–3·37 for ventilatory ratio in replication cohort 2). Interpretation: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality. Funding: Amsterdam UMC.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/77472

Collections

Scopus 2021